Identification of Continuous Human B-Cell Epitopes in the VP35, VP40, Nucleoprotein and Glycoprotein of Ebola Virus

• Published in: PloS one Vol. 9; no. 6; p. e96360
• Main Authors: Becquart, Pierre, Mahlakõiv, Tanel, Nkoghe, Dieudonné, Leroy, Eric M.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.06.2014; Public Library of Science (PLoS)
• Subjects: Adaptive immunology; Adolescent; Adult; Amino Acid Sequence; Analysis; Antigenic determinants; Apoptosis; B-Lymphocytes - immunology; Biology and Life Sciences; Budding; Child; Crystal structure; Defects; Disease Outbreaks; Ebola virus; Ebolavirus; Ebolavirus - genetics; Ebolavirus - immunology; Epidemics; Epitopes; Epitopes - genetics; Epitopes - immunology; Female; Fever; Gabon; Genomes; Glycoproteins; Glycoproteins - chemistry; Glycoproteins - genetics; Glycoproteins - immunology; Health aspects; Hemorrhage; Hemorrhagic fever; Hemorrhagic Fever, Ebola - blood; Hemorrhagic Fever, Ebola - epidemiology; Hemorrhagic Fever, Ebola - virology; Hemorrhagic fevers; Hepatitis; Human health and pathology; Humans; Humoral immunity; Immune response (humoral); Immunity; Immunoglobulin G; Immunoglobulins; Immunology; Infection; Infections; Infectious diseases; Life Sciences; Lymphocytes B; Male; Medicine and Health Sciences; Memory; Microbiology and Parasitology; Molecular Sequence Data; Nucleocapsid Proteins; Nucleoproteins - genetics; Nucleoproteins - immunology; Outbreaks; Patients; Peptides; Phylogenetics; Proteins; RNA polymerase; Serogroup; Viral Core Proteins - genetics; Viral Core Proteins - immunology; Viral diseases; Virology; Virulence (Microbiology); Viruses; VP40 protein; Gabon; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096360

Ebola virus (EBOV) is a highly virulent human pathogen. Recovery of infected patients is associated with efficient EBOV-specific immunoglobulin G (IgG) responses, whereas fatal outcome is associated with defective humoral immunity. As B-cell epitopes on EBOV are poorly defined, we sought to identify specific epitopes in four EBOV proteins (Glycoprotein (GP), Nucleoprotein (NP), and matrix Viral Protein (VP)40 and VP35). For the first time, we tested EBOV IgG+ sera from asymptomatic individuals and symptomatic Gabonese survivors, collected during the early humoral response (seven days after the end of symptoms) and the late memory phase (7-12 years post-infection). We also tested sera from EBOV-seropositive patients who had never had clinical signs of hemorrhagic fever or who lived in non-epidemic areas (asymptomatic subjects). We found that serum from asymptomatic individuals was more strongly reactive to VP40 peptides than to GP, NP or VP35. Interestingly, anti-EBOV IgG from asymptomatic patients targeted three immunodominant regions of VP40 reported to play a crucial role in virus assembly and budding. In contrast, serum from most survivors of the three outbreaks, collected a few days after the end of symptoms, reacted mainly with GP peptides. However, in asymptomatic subjects the longest immunodominant domains were identified in GP, and analysis of the GP crystal structure revealed that these domains covered a larger surface area of the chalice bowl formed by three GP1 subunits. The B-cell epitopes we identified in the EBOV VP35, VP40, NP and GP proteins may represent important tools for understanding the humoral response to this virus and for developing new antibody-based therapeutics or detection methods.